Aldehyde-functionalized polyethers are generally stable in aqueous solution and are very reactive electrophiles which form reversible bonds to amine-functionalized reactants. These two properties are highly desirable for many applications. For example, aldehyde-functionalized polyethers, and in particular, aldehyde-functionalized polyethylene glycols are useful for protein conjugation, surface modification, and for the formation of hydrogel adhesives and sealants which are useful for medical applications. For the formation of hydrogel adhesives and sealants, an aldehyde-functionalized polyether is reacted with an amine-containing component to form a crosslinked polymeric matrix which acts a sealant.
Various methods are known in the art for the preparation of aldehyde-functionalized polyethers. For example, various oxidative reactions utilizing oxidizing agents such as manganese oxide, pyridinium chlorochromate, or dimethyl sulfoxide-acetic anhydride have been used to convert the terminal hydroxyl groups of polyethylene glycol to aldehyde groups. However, these oxidative reactions are not quantitative and may be accompanied by unwanted side reactions. Additionally, product purification is difficult. Aldehyde-functionalized polyethylene glycols have also been prepared from the diethyl acetal of α-bromoacetaldehyde and by reaction of the polyethylene glycol chloride derivative with the phenoxide of 4-hydroxy-benzaldehyde. Rosen et al. (U.S. Pat. No. 7,217,845) describe aldehyde-functionalized polyethylene glycols that are prepared by functionalizing polyethylene glycol ends with X—(CH2)n—CHO, where X is O or N and n is from 2 to 8. However, these methods typically result in low yields, require multiple steps, and/or yield a product that is difficult to purify.
Therefore, the need exists for aldehyde-functionalized polyethers that are easy to prepare, can be prepared with readily available reactants, and can be produced in high yield and in pure form.